Neutrophil antibodies to myeloperoxidase (MPO), (MPO-ANCAs: Anti-Neutrophil Cytoplasmic Antibodies), are associated with intractable angiitis such as crescent-forming nephritis, microscopic polyangiitis (MPA) and allergic angiitis (AGA, Churg-Straus Syndrome (CSS)). Further, since the MPO-ANCA titer in the serum of patients with these diseases correlates to the disease activity, MPO-ANCAs are used as specific markers of these diseases in the diagnosis and assessment of treatments (see, for example, Non-patent Document 1).
However, even when a MPO-ANCA is used as a marker, the titer of the MPO-ANCA in serum does not always agree with the pathology. Thus, it has been suggested that MPO-ANCA is not a sole factor which induces angiitis by acting on neutrophils and plays a role after the onset of angiitis and there rather may be other molecule or mechanism which induces angiitis. Accordingly, in recent years, discussions have been made with regard to the possibility that there is a target molecule of autoantibody other than neutrophil MPO. Consequently, there have been reports on involvement of several target molecules such as Lamp2 (see Non-patent Documents 2 and 3). In addition, attempts have been made to elucidate the activation mechanism of vascular endothelial cells by autoantibodies including MPO-ANCA as a mechanism for onset of angiitis and pathological development. To this day, it has been reported that the serums of angiitis patients showing positive for an autoantibody induce the expression of ICAM-1 in human umbilical vein endothelial cells (HUVECs) (see Non-patent Document 4) and that the anti-proteinase-3 autoantibody (PR3-ANCA) of Wegener's granulomatosis patients induces the expressions of ICAM-1 and VCAM-1 (see Non-patent Documents 5 and 6). However, there has been no report with regard to the direct effects of a MPO-ANCA on vascular endothelial cells. Therefore, it is still unclear as to whether or not a molecule other than MPO-ANCAs and Lamp2 antibodies is involved in the pathology of angiitis. Furthermore, since reactions caused by anti-mouse MPO antibody (rmMPO antibody) are observed in the same manner also in a MPO-deficient mouse, it has been suggested that a molecule other than MPO serves as a target in vascular endothelial cells. Moreover, although it has been reported that the serums and autoantibodies of angiitis patients activate HUVECs, the pathogenicity thereof and the acting molecule have not been clarified.
In addition, the present inventors have reported that an anti-rmMPO antibody (MPO-ANCA) activates mouse glomerular endothelial cells (mGECs). However, it is still unclear with regard to the factors that play a role in the pathology of angiitis other than MPO-ANCAs and Lamp2 antibodies.
Thus, at present, while there are suggestions on the presence of other factors that are involved in the pathology of angiitis in addition to MPO-ANCAs that are clinically used in diagnosis and the like of angiitis, the essence of such factors is not clear. As described in the above, the diagnosis and assessment of treatments by MPO-ANCAs do not necessarily perfectly reflect the actual pathology; therefore, identification of the factors other than MPO-ANCAs can potentially complement the diagnosis and the like by MPO-ANCAs or provide a novel clinical marker which serves as an alternative and it is of extreme significance in terms of clinical medicine. Here, the present inventors discovered protein M as a factor other than MPO-ANCAs.